The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24).

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

In vitroα-glucosidase inhibition by honeybush (Cyclopia genistoides) food ingredient extract-potential for dose reduction of acarbose through synergism.

Extracts of Cyclopia species are used as food ingredients. In vitroα-glucosidase (AG) inhibition by ultrafiltered C. genistoides extract, fractions enriched in xanthones (XEF) and benzophenones (BEF), as well as mangiferin, isomangiferin, 3-ß-d-glucopyranosyliriflophenone (I3G) and 3-ß-d-glucopyranosyl-4-O-ß-d-glucopyranosyliriflophenone (IDG) was determined with acarbose as positive control. XEF was more potent than the extract and BEF (IC50 = 43.3, 95.5 and 205.7 µg mL-1, respectively). Compounds demonstrated potency in the descending order: acarbose (IC50 = 44.3 µM) > mangiferin (102.2 µM) > isomangiferin (119.8 µM) > I3G (237.5 µM) > IDG (299.4 µM). The combination index (CI) was used to determine synergism (CI < 0.7) as demonstrated for combinations of acarbose with XEF, BEF or the respective compounds at 50% and 75% effect levels. The greatest potential acarbose dose reductions (>six-fold) across all effect levels were calculated for combinations of acarbose with mangiferin or isomangiferin, explaining the greater acarbose dose reduction potential of XEF vs. BEF. The effect of batch-to-batch variation (n = 10) of raw plant material on AG inhibition was quantified at a fixed concentration (160 µg mL-1). XEFs (xanthone content = 223-481 g kg-1) achieved AG inhibition of 63-72%, whereas BEFs (benzophenone content = 114-251 g kg-1) achieved AG inhibition of 26-34%, with weak linear correlation (R2 < 0.43) between target compound content of the fractions and their achieved AG inhibition. Thus, extract fractions of C. genistoides, enriched in xanthones and benzophenones, show potential in reducing the effective dose of acarbose required to prevent postprandial hyperglycaemia.

Electroacupuncture combined with acarbose improves insulin sensitivity via peroxisome proliferator-activated receptor γ activation and produces a stronger glucose-lowering effect than acarbose alone in a rat model of steroid-induced insulin resistance.

BACKGROUND: Previous studies have reported that electroacupuncture (EA) induces a glucose-lowering effect by improving insulin resistance (IR) and reduces plasma free fatty acid (FFA) levels in rats with steroid-induced insulin resistance (SIIR). In addition, EA can activate cholinergic nerves and stimulate endogenous opioid peptides to lower plasma glucose in streptozotocin-induced hyperglycemic rats. The aim of this study was to investigate the glucose-lowering effects of 15 Hz EA at bilateral ST36 in combination with acarbose (ACA). We hypothesized that EA combined with ACA would produce a stronger glucose-lowering effect than ACA alone. METHODS: In this study, normal Wistar rats and SIIR rats were randomly divided into two groups: ACA and ACA + EA. To explore the potential mechanisms underlying the glucose-lowering effect, plasma FFA/insulin and insulin transduction signal pathway proteins were assayed. RESULTS: Combined ACA + EA treatment had a greater glucose-lowering effect than ACA alone in normal Wistar rats (-45% ± 3% vs -19% ± 3%, p < 0.001) and SIIR model rats (-43% ± 2% vs -16% ± 6%, p < 0.001). A significant reduction in plasma FFA levels, improvement in homeostatic model assessment of IR (HOMA-IR) index (-48.9% ± 4.0%, p < 0.001) and insulin sensitivity index (102% ± 16.9%, p < 0.001), and significant increases in insulin receptor substrate 1, glucose transporter 4, and peroxisome proliferator-activated receptor γ protein expressions in skeletal muscle, were also observed in the ACA + EA group of SIIR rats. CONCLUSION: Combined EA and ACA therapy had a greater glucose-lowering effect than ACA monotherapy; this combined therapy could be more effective at improving IR in SIIR rats, which may be related to a reduction in plasma FFA levels and an elevation of insulin signaling proteins. Whether this combined therapy has an effect in type 2 diabetes mellitus (T2DM) patients still needs to be explored.

Impact of baseline characteristics on glycemic effects of add-on saxagliptin or acarbose to metformin therapy: Subgroup analysis of the SMART study in Chinese patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: This secondary analysis of the 24-week SMART study examined the efficacy of add-on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus, based on baseline characteristics. MATERIALS AND METHODS: Randomized patients (n = 481) were classified into subgroups based on their baseline age (<65, ≥65 years), body mass index (BMI; <24, 24-<28, ≥28 kg/m2 ), glycated hemoglobin (HbA1c; <8%, 8-<9%, 9-<10%, ≥10%) and renal function (creatinine clearance 50-<80, ≥80 mL/min). Treatment effects on primary outcome (HbA1c) and key secondary outcomes of fasting plasma glucose (FPG), 2-h postprandial glucose and homeostatic model assessment of ß-cell function were assessed across patient subgroups. RESULTS: For saxagliptin, reductions in HbA1c from baseline to week 24 were consistent across different subgroups regardless of baseline age, body mass index, HbA1c and renal function (range -0.66 to -1.16%). Saxagliptin was associated with consistent reductions in FPG (-0.60 to -1.33 mmol/L) and 2-h postprandial glucose (-0.48 to -1.95 mmol/L) across the majority of subgroups studied. The efficacy of acarbose on FPG attenuated progressively with increasing baseline HbA1c (+0.86 to -1.43 mmol/L); an increase from baseline FPG was observed in patients with HbA1c >9%. The effect of acarbose on postprandial glucose was also variable (+0.23 to -3.38 mmol/L). CONCLUSIONS: As add-on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, body mass index and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%).

Effects of acarbose and metformin on the inflammatory state in newly diagnosed type 2 diabetes patients: a one-year randomized clinical study.

OBJECTIVE: This study aimed to investigate the changes in inflammatory biomarkers between newly diagnosed type 2 diabetes (T2DM) patients under one-year acarbose treatments and those under metformin managements. METHODS: Seventy patients with newly diagnosed T2DM and 32 volunteers with normal glucose tolerance (normal controls, NCs) were enrolled. Seventy patients with T2DM were randomly assigned to two subgroups and treated with acarbose (n=34) or metformin (n=36) for 1 year. Blood glucose, insulin, glycosylated hemoglobin (A1C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and inflammatory biomarker levels (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), and ferritin) were detected at 0, 6 and 12 months. RESULTS: After adjusting for sex, the waist-to-hip ratio (WHR) and body mass index (BMI), higher fasting plasma glucose (FPG), standard meal test 1/2 hr and 2 hr glucose, TG, TC, LDL-C, IL-6, TNF-α, IL-2 and ferritin levels were observed in T2DM group than in NCs (P<0.05). After 6 months of treatment, TNF-α levels were significantly decreased in both subgroups, and IL-6 and ferritin levels were significantly decreased after 12 months (P<0.05). However, no significant differences in the IL-6, TNF-α and ferritin levels were observed between the two subgroups. Moreover, significantly higher IL-6 and TNF-α levels were detected in the T2DM group than in NCs after 12 months of treatment (P<0.05). CONCLUSION: Patients with newly diagnosed T2DM exhibited a marked chronic inflammatory state characterized by increased IL-6, TNF-α, IL-1ß, IL-2 and ferritin levels. After 1 year of treatment with acarbose or metformin, IL-6, TNF-α, IL-1ß and ferritin levels were significantly decreased compared with the baseline. The anti-inflammatory effects of acarbose and metformin were comparable and required a long-term treatment (1 year), but the characteristics were different. Further investigations are needed to determine whether this effect was independent of the hypoglycemic effects.

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies.

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Pharmacoeconomic evaluation of glimepiride combined with other drugs in the treatment of diabetes.

The goal of diabetic drug treatment is to stabilize the blood sugar for a long time to close to the normal level, to correct the metabolic disorder and eliminate the symptoms. At present, glimepiride has become commonly used drugs for the treatment of diabetes with obesity. Compared with metformin, acarbose and rosiglitazone, glimepiride has different mechanisms of drug action, clinical combination showed synergistic hypoglycemic effect, good clinical curative effect. So, we use three treatments to study as group A (glimepiride and metformin); group B (glimepiride and acarbose); Group C (glimepiride and rosiglitazone). From the analysis of drug economics, glimepiride and metformin scheme is better, has the lowest cost per unit cost effect. From the comparison of scheme is efficient, the best curative effect is rosiglitazone plus glimepiride, effective rate as 96.7%. At the same time, the drug can be rationally used to reduce the occurrence of some drug-induced diseases and adverse drug reactions.

Rumen microbial and fermentation characteristics are affected differently by acarbose addition during two nutritional types of simulated severe subacute ruminal acidosis in vitro.

Little information is available on whether or not the effect of an alpha-glucosidase inhibitor on the prevention of ruminal acidosis is influenced by the type of diet during ruminant feeding. This study was conducted to explore the effect of acarbose addition on the prevention of severe subacute ruminal acidosis induced by either cracked wheat or beet pulp in vitro. Cracked wheat and beet pulp were fermented in vitro by rumen microorganisms obtained from three dairy cows. When cracked wheat was used as the substrate and fermented for 24 h, compared with the control, acarbose addition decreased the concentrations of acetate, propionate, butyrate, total volatile fatty acids, and lactate (P < 0.05), while linearly increased the ratio of acetate to propionate, pH value, and the ammonia-nitrogen level (P < 0.05). Applying Illumina MiSeq sequencing of a fragment of the 16S rRNA gene revealed that the relative abundance of Firmicutes and Bacteroidetes as well as the ACE (abundance-based coverage estimator) value, Chao 1 value, and Shannon index increased significantly (P < 0.05), while there was a significant reduction (P < 0.05) in the relative abundance of Tenericutes as well as Proteobacteria after adding acarbose compared to the control. On the other hand, when beet pulp was used as the substrate, acarbose addition had no significant effects (P > 0.05) on the fermentation parameters and the Chao 1 value, the Shannon index, and the proportion of Firmicutes and Bacteroidetes. In general, these findings indicate that acarbose had more effects on ruminal fermentation when wheat was used as the substrate, whereas it exhibited little effect on ruminal fermentation when beet pulp was used as the substrate.

Synergistic effects of acarbose and an Oroxylum indicum seed extract in streptozotocin and high-fat-diet induced prediabetic mice.

Prediabetes is defined as blood glucose levels above normal but below diabetes thresholds, and up to 70% of individuals with prediabetes will eventually develop diabetes if left untreated. Acarbose, the first FDA approved anti-prediabetes agent, has some disadvantages, such as reducing the risk of diabetes by only 36%, side effects and limited effects on complications. The aim of this study is to develop a new agent to treat prediabetes and to investigate the anti-prediabetes effects and mechanisms of acarbose and an Oroxylum indicum seed extract (OISE) in prediabetic mice. The combined drugs can reduce the dose of acarbose by 80% and reduce the risk of diabetes by 75%, which is one fold higher than acarbose monotherapy. The combined drugs showed synergistic anti-prediabetes effects and could be effective in preventing the complications of prediabetes. The combined drugs could improve glucose tolerance, improve lipid metabolism and reduce oxidative stress and tissue damage. For the mechanisms, the combined drugs can reduce synergistically postprandial hyperglycaemia by inhibiting α-glucosidase. Furthermore, baicalein in OISE was demonstrated to be a major component in reducing oxidative stress and chrysin was the primary compound that activated PPARγ.

Oral anti-diabetic pharmacological therapies for the treatment of women with gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major public health issue with rates increasing globally. Gestational diabetes, glucose intolerance first recognised during pregnancy, usually resolves after birth and is associated with short- and long-term complications for the mother and her infant. Treatment options can include oral anti-diabetic pharmacological therapies. OBJECTIVES: To evaluate the effects of oral anti-diabetic pharmacological therapies for treating women with GDM. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 May 2016), ClinicalTrials.gov, WHO ICTRP (14 May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included published and unpublished randomised controlled trials assessing the effects of oral anti-diabetic pharmacological therapies for treating pregnant women with GDM. We included studies comparing oral anti-diabetic pharmacological therapies with 1) placebo/standard care, 2) another oral anti-diabetic pharmacological therapy, 3) combined oral anti-diabetic pharmacological therapies. Trials using insulin as the comparator were excluded as they are the subject of a separate Cochrane systematic review.Women with pre-existing type 1 or type 2 diabetes were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data and data were checked for accuracy. MAIN RESULTS: We included 11 studies (19 publications) (1487 women and their babies). Eight studies had data that could be included in meta-analyses. Studies were conducted in Brazil, India, Israel, UK, South Africa and USA. The studies varied in diagnostic criteria and treatment targets for glycaemic control for GDM. The overall risk of bias was 'unclear' due to inadequate reporting of methodology. Using GRADE the quality of the evidence ranged from moderate to very low quality. Evidence was downgraded for risk of bias (reporting bias, lack of blinding), inconsistency, indirectness, imprecision and for oral anti-diabetic therapy versus placebo for generalisability. Oral anti-diabetic pharmacological therapies versus placebo/standard careThere was no evidence of a difference between glibenclamide and placebo groups for hypertensive disorders of pregnancy (risk ratio (RR) 1.24, 95% confidence interval (CI) 0.81 to 1.90; one study, 375 women, very low-quality evidence), birth by caesarean section (RR 1.03, 95% CI 0.79 to 1.34; one study, 375 women, very low-quality evidence), perineal trauma (RR 0.98, 95% CI 0.06 to 15.62; one study, 375 women, very low-quality evidence) or induction of labour (RR 1.18, 95% CI 0.79 to 1.76; one study, 375 women; very low-quality evidence). No data were reported for development of type 2 diabetes or other pre-specified GRADE maternal outcomes (return to pre-pregnancy weight, postnatal depression). For the infant, there was no evidence of a difference in the risk of being born large-for-gestational age (LGA) between infants whose mothers had been treated with glibenclamide and those in the placebo group (RR 0.89, 95% CI 0.51 to 1.58; one study, 375, low-quality evidence). No data were reported for other infant primary or GRADE outcomes (perinatal mortality, death or serious morbidity composite, neurosensory disability in later childhood, neonatal hypoglycaemia, adiposity, diabetes). Metformin versus glibenclamideThere was no evidence of a difference between metformin- and glibenclamide-treated groups for the risk of hypertensive disorders of pregnancy (RR 0.70, 95% CI 0.38 to 1.30; three studies, 508 women, moderate-quality evidence), birth by caesarean section (average RR 1.20, 95% CI 1.20; 95% CI 0.83 to 1.72, four studies, 554 women, I2 = 61%, Tau2 = 0.07 low-quality evidence), induction of labour (0.81, 95% CI 0.61 to 1.07; one study, 159 women; low-quality evidence) or perineal trauma (RR 1.67, 95% CI 0.22 to 12.52; two studies, 158 women; low-quality evidence). No data were reported for development of type 2 diabetes or other pre-specified GRADE maternal outcomes (return to pre-pregnancy weight, postnatal depression). For the infant there was no evidence of a difference between the metformin- and glibenclamide-exposed groups for the risk of being born LGA (average RR 0.67, 95% CI 0.24 to 1.83; two studies, 246 infants, I2 = 54%, Tau2 = 0.30 low-quality evidence). Metformin was associated with a decrease in a death or serious morbidity composite (RR 0.54, 95% CI 0.31 to 0.94; one study, 159 infants, low-quality evidence). There was no clear difference between groups for neonatal hypoglycaemia (RR 0.86, 95% CI 0.42 to 1.77; four studies, 554 infants, low-quality evidence) or perinatal mortality (RR 0.92, 95% CI 0.06 to 14.55, two studies, 359 infants). No data were reported for neurosensory disability in later childhood or for adiposity or diabetes. Glibenclamide versus acarboseThere was no evidence of a difference between glibenclamide and acarbose from one study (43 women) for any of their maternal or infant primary outcomes (caesarean section, RR 0.95, 95% CI 0.53 to 1.70; low-quality evidence; perinatal mortality - no events; low-quality evidence; LGA , RR 2.38, 95% CI 0.54 to 10.46; low-quality evidence). There was no evidence of a difference between glibenclamide and acarbose for neonatal hypoglycaemia (RR 6.33, 95% CI 0.87 to 46.32; low-quality evidence). There were no data reported for other pre-specified GRADE or primary maternal outcomes (hypertensive disorders of pregnancy, development of type 2 diabetes, perineal trauma, return to pre-pregnancy weight, postnatal depression, induction of labour) or neonatal outcomes (death or serious morbidity composite, adiposity or diabetes). AUTHORS' CONCLUSIONS: There were insufficient data comparing oral anti-diabetic pharmacological therapies with placebo/standard care (lifestyle advice) to inform clinical practice. There was insufficient high-quality evidence to be able to draw any meaningful conclusions as to the benefits of one oral anti-diabetic pharmacological therapy over another due to limited reporting of data for the primary and secondary outcomes in this review. Short- and long-term clinical outcomes for this review were inadequately reported or not reported. Current choice of oral anti-diabetic pharmacological therapy appears to be based on clinical preference, availability and national clinical practice guidelines.The benefits and potential harms of one oral anti-diabetic pharmacological therapy compared with another, or compared with placebo/standard care remains unclear and requires further research. Future trials should attempt to report on the core outcomes suggested in this review, in particular long-term outcomes for the woman and the infant that have been poorly reported to date, women's experiences and cost benefit.

[Hypoglycemia due to antibodies to exogenous insulin in a patient with type 2 diabetes ­ a case report of treatment with new generation oral hypoglycemic agents].

Hypoglycemic syndromes associated with immune reactions against insulin are rare phenomena described predominantly in Asians. Steroid therapy, immunosuppression or plasmapheresis is often required. Case report: A 73-year-old White woman with a 20-year history of type 2 diabetes was admitted to hospital due to recurrent incidents of hypoglycemia that started several months after insulin initiation (lispro 75/25) and increased in severity over the next 5 years. They were accompanied by postprandial hyperglycemia up to 25 mmol/l. The patient's glycated hemoglobin (HbA1c) was 70 mmol/ mol (8.6%). During hypoglycemic episodes recorded serum C-peptide was 0.57-0.73 nmol/l (1.7-2.2 ng/ml), while insulin concentration exceeded 7000 pmol/l (1000 mIU/l). Surreptitious insulin administration was ruled out as was, based on diagnostic imaging, the presence of an insulin secreting tumor. Anti-insulin antibody (AIA) level measured by 125I-insulin binding method was 92.5% (normal < 8.2%). Hypoglycemic episodes occurred for four days after discontinuation of insulin therapy and then resolved completely. Good glycemic control was maintained with metformin, acarbose and dapagliflozin. Three months later dapagliflozin was replaced with vildagliptine due to poor tolerance of a SGLT-2 inhibitor. Patient's HbA1c was 54 mmol/mol (7.1%), total fasting insulin level 2577 pmol/l and AIA binding 85.9%. Over the next year the patient has not experienced hypoglycemia and maintained good glycemic control, as HbA1c level was 53 mmol/l (7.0%) and AIA binding 39.5%. Conclusions: In this rare case of a patient with diabetes and hypoglycemic syndrome related to AIA, we achieved a rapid and stable remission of hypoglycemia without immunosuppression. Good glycemic control, despite 20-year history of diabetes was achieved with oral hypoglycemic agents.

Cost-Effectiveness of Dapagliflozin versus Acarbose as a Monotherapy in Type 2 Diabetes in China.

OBJECTIVE: To estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs. Health insurance costs (2015¥) were estimated over 40 years from a healthcare payer perspective. Univariate and probabilistic sensitivity analyses were performed. RESULTS: The model predicted that dapagliflozin had lower incidences of cardiovascular events, hypoglycemia and mortality events, was associated with a mean incremental benefit of 0.25 quality-adjusted life-years (QALYs) and with a lower cost of ¥8,439 compared with acarbose. This resulted in a cost saving of ¥33,786 per QALY gained with dapagliflozin. Sensitivity analyses determined that the results are robust. CONCLUSION: Dapagliflozin is dominant compared with acarbose as monotherapy for Chinese T2DM patients, with a little QALY gain and lower costs. Dapagliflozin offers a well-tolerated and cost-effective alternative medication for treatment-naive patients in China, and may have a direct impact in reducing the disease burden of T2DM.

Retrospective comparison of voglibose or acarbose as an add-on therapy to sulfonylureas in Western Indian patients with uncontrolled overweight/obese type 2 diabetes.

AIM: The study was aimed to investigate the effect of voglibose or acarbose as an add-on treatment in overweight/obese type 2 diabetes (T2DM) patients who are uncontrolled with metformin and sulfonylureas (SUs) in Western part of India. PARTICIPANTS AND METHODS: A retrospective study included 77 participants (BMI≥25kg/m(2); HbA1c level>8% and<9.5%) with overweight/obese T2DM. These participants were treated with either voglibose or acarbose. Glycemic parameters (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI and lipid parameters were evaluated at baseline, 3-month, 6-month and 9-month of treatment. Adverse events were also captured at respective time points. RESULTS: Voglibose showed significant reduction in HbA1c and bodyweight with short duration of treatment (6 months; P<0.05 and 9 months; P<0.01) whereas acarbose showed significant reduction with longer duration of treatment (9 months; P<0.05) when compared with baseline. Moreover, both treatment groups were reported with reduction in BMI. Further, significant improvement in lipid parameters except LDL and HDL were observed in both treatment groups when compared with baseline. None of participant was discontinued due to side effects of the treatment. In addition, the frequency of hypoglycemia was decreased in both treatment groups. CONCLUSION: Voglibose or acarbose as an add-on treatment with metformin and sulfonylureas in uncontrolled obese/overweight T2DM provides desired glycemic control, reduces bodyweight and improves lipid parameters with good tolerability profile.

Factors that influence the efficacy of acarbose and metformin as initial therapy in Chinese patients with newly diagnosed type 2 diabetes: a subanalysis of the MARCH trial.

OBJECTIVE: To conduct a subanalysis of the randomized MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment) trial to investigate whether specific characteristics are associated with the efficacy of either acarbose or metformin as initial therapy. RESEARCH DESIGN AND METHODS: A total of 657 type 2 diabetes patients who were randomly assigned to 48 weeks of therapy with either acarbose or metformin in the MARCH trial were divided into two groups based upon their hemoglobin A1c (HbA1c) levels at the end of follow-up: HbA1c <7% (<53 mmol/mol) and ≥7% (≥53 mmol/mol). Univariate, multivariate, and stepwise linear regression analyses were applied to identify the factors associated with treatment efficacy. MAIN OUTCOME MEASURES: Because this was a subanalysis, no measurement was performed. RESULTS: Univariate analysis showed that the efficacy of acarbose and metformin was influenced by HbA1c, fasting blood glucose (FBG), and 2 hour postprandial venous blood glucose (2hPPG) levels, as well as by changes in body mass index (BMI) (p ≤ 0.006). Multivariate analysis and stepwise linear regression analyses indicated that lower baseline 2hPPG values and greater changes in BMI were factors that positively influenced efficacy in both treatment groups (p ≤ 0.05). Stepwise regression model analysis also revealed that a lower baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR) and higher serum insulin area under the curve (AUC) were factors positively influencing HbA1c normalization in all patients (p ≤ 0.032). CONCLUSIONS: Newly diagnosed type 2 diabetes patients with lower baseline 2hPPG and HOMA-IR values are more likely to achieve glucose control with acarbose or metformin treatment. Furthermore, the change in BMI after acarbose or metformin treatment is also a factor influencing HbA1c normalization. A prospective study with a larger sample size is necessary to confirm our results as well as measure ß cell function and examine the influence of the patients' dietary habits.

Saxagliptin is similar in glycaemic variability more effective in metabolic control than acarbose in aged type 2 diabetes inadequately controlled with metformin.

This study compared the effects on glycaemic variability and glucose control between saxagliptin and acarbose as add-on therapies for aged T2DM inadequately controlled with metformin alone. The results showed that compared with acarbose-metformin, saxagliptin-metformin was more effective in glucose control with similar glycaemic variability.

Study of Antiglycation, Hypoglycemic, and Nephroprotective Activities of the Green Dwarf Variety Coconut Water (Cocos nucifera L.) in Alloxan-Induced Diabetic Rats.

Coconut water (CW) is a natural nutritious beverage, which contains several biologically active compounds that are traditionally used in the treatment of diarrhea and rehydration. Several works with CW have been related with antioxidant activity, which is very important in the diabetic state. To evaluate the hypoglycemic and nephroprotective activities of CW, alloxan-induced diabetic rats were pre- and post-treated by gavage with CW (3 mL/kg), caffeic acid (CA) (10 and 15 mg/kg), and acarbose (Acb) (714 µg/kg) during a period of 16 days. Body weight, blood glucose, glycated hemoglobin (HbA1c), and Amadori products in plasma and kidney homogenates were evaluated in all groups and used as parameters for the monitoring of the diabetic state. The results showed that rats of the CW+diabetic group had maintenance in blood glucose compared with the control group (P<.05) in addition to a decrease of HbA1c levels and increase of body weight when compared with the diabetic group rats (P<.05). The animals of the CA and CA+diabetic groups did not have significant variation of body weight (P<.05) during the experiment; however, they showed decrease in their HbA1c and urea levels in plasma as well as Amadori products in kidney homogenates when compared with the diabetic group (P<.05). Our results indicate that CW has multiple beneficial effects in diabetic rats for preventing hyperglycemia and oxidative stress caused by alloxan.

MARCH2: comparative assessment of therapeutic effects of acarbose and metformin in newly diagnosed type 2 diabetes patients.

BACKGROUND: The data of MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycaemic treatment) trial demonstrated that acarbose and metformin have similar efficacy as initial therapy for hemoglobin A1c (HbA1c) reduction in Chinese patients with newly diagnosed type 2 diabetes. We investigated whether the therapeutic efficacy was diversified under different body mass index (BMI) status. METHODS: All 784 subjects were divided into normal-weight group (BMI<24 kg/m2), overweight group (BMI 24-28 kg/m2) and obese group (BMI≥28 kg/m2). Patients were assigned to 48 weeks of therapy with acarbose or metformin, respectively. The clinical trial registry number was ChiCTR-TRC-08000231. RESULTS: The reduction of HbA1c levels and the proportion of patients with HbA1c of 6.5% or less were similar in the three groups after acarbose and metformin treatment. In overweight group, fasting blood glucose (FBG) after metformin treatment showed greater decline compared to acarbose group at 48 weeks [-1.73 (-1.99 to -1.46) vs. -1.37 (-1.61 to -1.12), P<0.05), however the decrease of 2 h post-challenge blood glucose (PBG) after acarbose treatment at 48 weeks was bigger compared to metformin group [-3.34 (-3.83 to-2.84) vs. -2.35 (-2.85 to -1.85), P<0.01]. Both acarbose and metformin treatment resulted in a significant decrease in waist circumference, hip circumference, weight and BMI in the three groups (all P<0.05). CONCLUSION: Acarbose and metformin decreased HbA1c levels similarly regardless of BMI status of Chinese type 2 diabetic patients. Acarbose and metformin resulted in a significant and modest improvement of anthropometric parametres in different BMI status. Thus, acarbose treatment may contribute a similar effect on plasma glucose control compared to metformin, even in obesity patients. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-08000231.

Alpha glucosidase inhibitors.

Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action. Working to delay carbohydrate absorption in the gastrointestinal tract, they control postprandial hyperglycaemia and provide unquestioned cardiovascular benefit. Specially suited for a traditional Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds' of diabetology. The use of these oral antidiabetic drugs (OADs) that target pathophysiology in the early stages of type 2 diabetes, notably to reduce postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with time. This review describes the history of their development, mechanism of action, basic and clinical pharmacology, and suggests practical, evidence-based guidance for their optimal use.

Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial.

BACKGROUND: Metformin is the only first-line oral hypoglycaemic drug for type 2 diabetes recommended by international guidelines with proven efficacy, safety, and cost-effectiveness. However, little information exists about its use in Asian populations. We aimed to ascertain the effectiveness of the α-glucosidase inhibitor acarbose, extensively adopted in China, compared with metformin as the alternative initial therapy for newly diagnosed type 2 diabetes. METHODS: In this 48-week, randomised, open-label, non-inferiority trial, patients who were newly diagnosed with type 2 diabetes, with a mean HbA1c of 7·5%, were enrolled from 11 sites in China. After a 4-week lifestyle modification run-in, patients were assigned to 24 weeks of monotherapy with metformin or acarbose as the initial treatment, followed by a 24-week therapy phase during which add-on therapy was used if prespecified glucose targets were not achieved. Primary endpoints were to establish whether acarbose was non-inferior to metformin in HbA1c reduction at week 24 and week 48 timepoints. The non-inferiority margin was 0·3%, with an expected null difference in the change from baseline to week 48 in HbA1c. Analysis was done on a modified intention-to-treat population. This study was registered with Chinese Clinical Trial Registry, number ChiCTR-TRC-08000231. FINDINGS: Of the 788 patients randomly assigned to treatment groups, 784 patients started the intended study drug. HbA1c reduction at week 24 was -1·17% in the acarbose group and -1·19% in the metformin group. At week 48, the HbA1c reduction was -1·11% (acarbose) and -1·12% (metformin) with difference 0·01% (95% CI -0·12 to 0·14, p=0·8999). Six (2%) patients in the acarbose group and seven (2%) patients in the metformin group had serious adverse events, and two (1%) and four (1%) had hypoglycaemic episodes. INTERPRETATION: This study provides evidence that acarbose is similar to metformin in efficacy, and is therefore a viable choice for initial therapy in Chinese patients newly diagnosed with type 2 diabetes. FUNDING: Bayer Healthcare (China) and Double Crane Phama.